Synthesis method of 2,3-dimethyl-4-nitropyridine-N-oxide

Abstract

The invention discloses a synthesis method of 2,3-dimethyl-4-nitropyridine-N-oxide and belongs to the field of chemical industry. The synthesis method comprises the following steps: mixing 2,3-dimethylpyridine-N-oxide with thickened sulfuric acid to form a mixed solution, and dropwise adding the sulfuric acid solution of potassium nitrate to the mixed solution under the condition that the temperature ranges from -10 DEG C to 20 DEG C; after finishing the dropwise addition, reacting under the condition that the temperature ranges from 80 DEG C to 120 DEG C. According to the synthesis method, as potassium nitrate is taken as a nitration reagent to take the place of thickened nitric acid or fuming nitric acid, the reaction time is greatly shortened, no brown yellow smoke is generated in the reaction and after-treatment processes, the operating environment is friendly, the environmental pollution problem caused by the use of a large quantity of nitric acid is reduced, and meanwhile, the reaction yield is also increased to a certain extent; in today when the environmental problem is increasingly emphasized, potassium nitrate can be applied to complete the nitration reaction well instead of nitric acid.

Description

technical field

[0001] The invention belongs to the field of chemical industry, and in particular relates to a synthesis method of 2,3-dimethyl-4-nitropyridine-N-oxide. Background technique

[0002] 2,3-Dimethyl-4-nitropyridine-N-oxide is an important pharmaceutical intermediate, which can be used to synthesize lansoprazole and rabeprazole. Use 2,3-lutidine as the starting material, add hydrogen peroxide and a suitable catalyst to obtain 2,3-lutidine-N-oxide, and then nitrate with concentrated nitric acid / sulfuric acid or fuming nitric acid. Sulfuric acid as a mixed acid Reagent to produce 2,3-dimethyl-4-nitropyridine-N-oxide.

[0003] Concentrated sulfuric acid plays a catalytic and dehydrating role in the nitration reaction. When the concentrated nitric acid of 65%~68% is adopted as the nitrating reagent, due to the high water content in the concentrated nitric acid, the reaction is affected in the presence of water, resulting in a decrease in the yield and a decrease in...

Examples

Embodiment 1

[0019] Dissolve 12.3g of 2,3-lutidine-N-oxide in 92g of concentrated sulfuric acid (mass concentration: 98%), and add potassium nitrate sulfuric acid dropwise at a temperature of -10°C to -5°C solution (14.15 g of potassium nitrate, 100 g of concentrated sulfuric acid with a mass concentration of 98%). After the dropwise addition was completed, the reaction was carried out at a temperature of 80° C. to 85° C. for 2 hours. HPLC monitoring until complete reaction of starting material. Cool down to room temperature, add water, stir, and filter. The filtrate was extracted three times with dichloromethane, and the organic phase was concentrated to obtain 15.6 g of light yellow 2,3-dimethyl-4-nitropyridine-N-oxide, with an HPLC purity of 99% and a yield of 92.9%.

Embodiment 2

[0021] 12.3g of 2,3-lutidine-N-oxide was dissolved in 188g of concentrated sulfuric acid (98% mass concentration), and the sulfuric acid solution of potassium nitrate (nitric acid Potassium 40.44g, mass concentration is 98% concentrated sulfuric acid 600g). After the dropwise addition was completed, the reaction was carried out at a temperature of 110° C. to 120° C. for 0.5 hours. HPLC monitoring until complete reaction of starting material. Cool down to room temperature, add water, stir, and filter. The filtrate was extracted three times with dichloromethane, and the organic phase was concentrated to obtain 15.5 g of light yellow 2,3-dimethyl-4-nitropyridine-N-oxide, with an HPLC purity of 99% and a yield of 92.3%.

Embodiment 3

[0023] Dissolve 12.3g of 2,3-lutidine-N-oxide in 65g of concentrated sulfuric acid (mass concentration is 98%), add dropwise sulfuric acid solution of potassium nitrate (nitric acid Potassium 10.11g, mass concentration is 98% concentrated sulfuric acid 60g). After the dropwise addition is completed, the reaction is carried out at a temperature of 85° C. to 90° C. for 1 hour. HPLC monitoring until complete reaction of starting material. Cool down to room temperature, add water, stir, and filter. The filtrate was extracted three times with dichloromethane, and the organic phase was concentrated to obtain 15.3 g of light yellow 2,3-dimethyl-4-nitropyridine-N-oxide, with a HPLC purity of 99% and a yield of 91.1%.

technical field

[0001] The invention belongs to the field of chemical industry, and in particular relates to a synthesis method of 2,3-dimethyl-4-nitropyridine-N-oxide. Background technique

[0002] 2,3-Dimethyl-4-nitropyridine-N-oxide is an important pharmaceutical intermediate, which can be used to synthesize lansoprazole and rabeprazole. Use 2,3-lutidine as the starting material, add hydrogen peroxide and a suitable catalyst to obtain 2,3-lutidine-N-oxide, and then nitrate with concentrated nitric acid / sulfuric acid or fuming nitric acid. Sulfuric acid as a mixed acid Reagent to produce 2,3-dimethyl-4-nitropyridine-N-oxide.

[0003] Concentrated sulfuric acid plays a catalytic and dehydrating role in the nitration reaction. When the concentrated nitric acid of 65%~68% is adopted as the nitrating reagent, due to the high water content in the concentrated nitric acid, the reaction is affected in the presence of water, resulting in a decrease in the yield and a decrease in...

Examples

Embodiment 1

[0019] Dissolve 12.3g of 2,3-lutidine-N-oxide in 92g of concentrated sulfuric acid (mass concentration: 98%), and add potassium nitrate sulfuric acid dropwise at a temperature of -10°C to -5°C solution (14.15 g of potassium nitrate, 100 g of concentrated sulfuric acid with a mass concentration of 98%). After the dropwise addition was completed, the reaction was carried out at a temperature of 80° C. to 85° C. for 2 hours. HPLC monitoring until complete reaction of starting material. Cool down to room temperature, add water, stir, and filter. The filtrate was extracted three times with dichloromethane, and the organic phase was concentrated to obtain 15.6 g of light yellow 2,3-dimethyl-4-nitropyridine-N-oxide, with an HPLC purity of 99% and a yield of 92.9%.

Embodiment 2

[0021] 12.3g of 2,3-lutidine-N-oxide was dissolved in 188g of concentrated sulfuric acid (98% mass concentration), and the sulfuric acid solution of potassium nitrate (nitric acid Potassium 40.44g, mass concentration is 98% concentrated sulfuric acid 600g). After the dropwise addition was completed, the reaction was carried out at a temperature of 110° C. to 120° C. for 0.5 hours. HPLC monitoring until complete reaction of starting material. Cool down to room temperature, add water, stir, and filter. The filtrate was extracted three times with dichloromethane, and the organic phase was concentrated to obtain 15.5 g of light yellow 2,3-dimethyl-4-nitropyridine-N-oxide, with an HPLC purity of 99% and a yield of 92.3%.

Embodiment 3

[0023] Dissolve 12.3g of 2,3-lutidine-N-oxide in 65g of concentrated sulfuric acid (mass concentration is 98%), add dropwise sulfuric acid solution of potassium nitrate (nitric acid Potassium 10.11g, mass concentration is 98% concentrated sulfuric acid 60g). After the dropwise addition is completed, the reaction is carried out at a temperature of 85° C. to 90° C. for 1 hour. HPLC monitoring until complete reaction of starting material. Cool down to room temperature, add water, stir, and filter. The filtrate was extracted three times with dichloromethane, and the organic phase was concentrated to obtain 15.3 g of light yellow 2,3-dimethyl-4-nitropyridine-N-oxide, with a HPLC purity of 99% and a yield of 91.1%.

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